PROJECT SUMMARY/ABSTRACT The University of Texas Southwestern Medical Center (UTSW), one of the premier academic medical centers in the world, requests continued support for a graduate and post-graduate Molecular Microbiology Training Program (MMTP) that has existed for 20 years. This MMTP supports five predoctoral students and two postdoctoral fellows for two-year training periods each. A particularly attractive feature of this highly successful training program has been its departure from conventional program- or departmental-based training to an interdisciplinary program that maintains a strong microbiology orientation while, at the same time, broadens the scope of the training mission to include many other aspects of molecular and cell biology. The highly diverse backgrounds of the 28 trainers, comprised of a core group of highly accomplished established investigators and an expanding, impressive new faculty, embody interdisciplinary research programs bound by the common theme of molecular and cellular microbiology. The training faculty emanate from 10 different departments/centers (Microbiology, Immunology, Physiology, Internal Medicine/Infectious Diseases, Comprehensive Cancer Center, Cell Biology, Molecular Biology, Pharmacology, Biochemistry, and Pediatrics). The MMTP serves as a primary focus for formal interactions among this overlapping group of talented trainers who have strong records of accomplishment in research and training. Our goal is to train students and fellows for research careers in the general areas of the molecular basis of microbial pathogenesis, cellular microbiology, host defense mechanisms, vaccine development, regulation of virulence expression, pathogen adaptation, drug development, structural biology, and many other related areas. The research interests of the majority of the faculty include bacterial and viral pathogenesis, microbial toxins, quorum sensing, innate and adaptive immune mechanisms, antimicrobial drug design, autophagy, oncogenesis, RNA metabolism, bacterial type III secretion systems, vaccine development, translational science, microbial physiology, viral evolution, and structural biology (as it pertains to microbial pathogenesis). There is a strong emphasis on molecular mechanisms, molecular biology, and the application of the most contemporary methods in molecular technologies (e.g., structural biology, biochemistry, and molecular biophysics), all of which provide the thread that unites and integrates the diverse research areas. Trainees who complete this program are expected to be able to apply state-of-the-art molecular approaches towards important problems in the microbiological sciences and for the improvement of preventive and/or therapeutic intervention strategies for infectious diseases. There is solid evidence of major successes for this training program over the past funding interval.